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Variegation and silencing in a lentiviral-based murine transgenic model.

par Baup, Delphine ;Fraga, Laurent;Pernot, Eileen ;Van Acker, Annette;Vanherck, Anne Sophie ;Breckpot, Karine;Thielemans, Kris M.;Schurmans, Stéphane ;Moser, Muriel ;Leo, Oberdan
Référence Transgenic research
Publication Publié, 2009-08

Article révisé par les pairs

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Résumé :

Lentiviral based constructs represent a recent development in the generation of transgenic animals. The ease of use, and the fact that the same backbone vectors can be used to down-modulate endogenous gene expression and to produce transgenic animals overexpressing a gene of interest, have fuelled growing interest in this technology. In this study, we have used a lentiviral delivery system to generate transgenic mice expressing altered levels (up or downregulated) of a gene of interest. Although this lentiviral-based approach led to high levels of transgenesis and germ line transmission, a wide variation in transgene expression was observed in most first and second generation mouse lines. In particular, despite the segregation of integrants into single-copy expressing mouse lines, transgene expression appeared to be the target of epigenetic regulatory mechanism, often causing the coexistence of high and low transgene expressing cells within a given tissue such as blood peripheral lymphocytes. The establishment and analysis of large number of mouse lines may therefore be required to select a stable transgenic line with pancellular expression of a gene of interest using this lentiviral-based approach.